During prolonged starvation (>5 days), the brain adapts to use ketone bodies as its primary fuel. The biochemical marker that BEST signals the shift of the brain to ketone utilisation at the enzyme level is:

• A Upregulation of glucose transporter GLUT1 in the blood-brain barrier
• B Activation of pyruvate dehydrogenase kinase 4 (PDK4), shifting acetyl-CoA to ketogenesis
• C Induction of succinyl-CoA:3-oxoacid CoA transferase (SCOT) in brain neurons ✓
• D Upregulation of beta-hydroxybutyrate dehydrogenase in hepatocytes

Explanation

SCOT (succinyl-CoA:3-oxoacid CoA transferase, also called 3-oxoacid CoA transferase) is the key enzyme that converts acetoacetate + succinyl-CoA to acetoacetyl-CoA + succinate in extrahepatic tissues including brain, enabling ketone body utilization. The liver lacks SCOT (which is why it cannot oxidize its own ketones). During prolonged starvation, neurons markedly upregulate SCOT expression, enabling ketone bodies to replace ~60–70% of glucose as brain fuel. PDK4 is activated in peripheral muscle/adipose, not brain, and it inhibits pyruvate dehydrogenase to preserve carbon for gluconeogenesis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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